Electrochemical sensors with carrier

ABSTRACT

An electrochemical sensing apparatus and methods are provided. In one embodiment, an apparatus is provided having a carrier that supports an electrochemical module and that communicates between electrodes on the electrochemical module and an analyte measurement device.

FIELD

The present disclosure relates to methods and systems for determininganalyte concentration of a sample.

BACKGROUND

Analyte detection in physiological fluids, e.g. blood or blood derivedproducts, is of ever increasing importance to today's society. Analytedetection assays find use in a variety of applications, includingclinical laboratory testing, home testing, etc., where the results ofsuch testing play a prominent role in diagnosis and management in avariety of disease conditions. Analytes of interest include glucose fordiabetes management, cholesterol, and the like. In response to thisgrowing importance of analyte detection, a variety of analyte detectionprotocols and devices for both clinical and home use have beendeveloped.

One type of method that is employed for analyte detection is anelectrochemical method. In such methods, an aqueous liquid sample isplaced into a sample-receiving chamber in an electrochemical cell thatincludes two electrodes, e.g., a counter and working electrode. Theanalyte is allowed to react with a redox reagent to form an oxidizable(or reducible) substance in an amount corresponding to the analyteconcentration. The quantity of the oxidizable (or reducible) substancepresent is then estimated electrochemically and related to the amount ofanalyte present in the initial sample.

The electrochemical cell is typically present on a test strip which isconfigured to electrically connect the cell to an analyte measurementdevice. While current test strips are effective, the size of the teststrips can directly impact the manufacturing costs. While it isdesirable to provide test strips having a size that facilitates handlingof the strip, increases in size will tend to increase manufacturingcosts where there is an increased amount of material used to form thestrip. Moreover, increasing the size of the test strip tends to decreasethe quantity of strips produced per batch, thereby further increasingmanufacturing costs.

Accordingly, there is a need for improved electrochemical sensingapparatus and methods.

SUMMARY

The present invention generally provides electrochemical sensingapparatus and methods. In one embodiment, an electrochemical sensingapparatus is provided and includes a carrier having first and secondelectrically conductive regions that are electrically isolated from oneanother. The carrier can also include an opening extending therethrough.The apparatus also includes an electrochemical module mounted betweenthe top and bottom portions of the carrier such that at least a portionof the electrochemical module extends across the opening. Theelectrochemical module includes an electrochemical cavity with a firstelectrode in electrical communication with the first conductive regionof the carrier, a second electrode in electrical communication with thesecond conductive region of the carrier, and a sample receiving chamberthat includes a reagent layer.

While the carrier can have a variety of configurations, in oneembodiment the carrier has a top portion carrying the first conductiveregion, and a bottom portion carrying the second conductive region infacing relationship with the first conductive region. The carrier can befolded along a fold line to define the top and bottoms portions. Theopening can be located anywhere on the carrier, but in an exemplaryembodiment the opening extends across the fold line and through thefirst and second conductive regions. Further, the opening can be locatedon a distal end of the carrier, and a proximal end of the carrier caninclude first and second contacts configured to establish a connectionbetween the first and second electrodes and a separate analytemeasurement device. The carrier can also include an adhesive disposedbetween the top and bottom portions of the carrier. The adhesive can beconfigured to maintain the top and bottom portions at a fixed distanceapart from one another and optionally to help to hold theelectrochemical module in place on the carrier.

The electrochemical module can also have a variety of configurations. Inone embodiment, the electrochemical module has a maximum length and amaximum width that is less than a maximum length and a maximum width ofthe carrier. In another embodiment, the electrochemical module can haveopposed ends engaged between the top and bottom portions of the carrier,and the sample receiving chamber can be located between the opposed endsand spaced a distance apart from the carrier. A sample inlet can belocated in the mid-portion of the electrochemical module such that theinlet is positioned outwardly from the opening in the carrier. In anexemplary embodiment, the electrochemical module includes a topinsulating substrate carrying the first electrode, a bottom insulatingsubstrate carrying the second electrode, and a spacer disposed betweenthe first and second electrodes and maintaining the first and secondelectrodes in a spaced apart relationship with one another. The top andbottom insulating substrates can be offset from one another such that aportion of the first electrode on the top insulating substrate is incontact with the first conductive region on the carrier, and a portionof the second electrode on the bottom insulating substrate is in contactwith the second conductive region on the carrier. In other aspects, theelectrochemical module can be non-rectangular and can have a centralportion extending along a central axis and containing theelectrochemical cavity, and opposed end portions that extend angularlyfrom the central portion such that each end portion has a central axisthat extends at an angle relative to the central axis of the centralportion.

In another embodiment, an electrochemical sensing apparatus is providedand includes a carrier having a first conductive area and a secondconductive area that is electrically isolated from the first conductivearea, and an opening formed through the carrier. The apparatus alsoincludes an electrochemical module mounted on the carrier such that atleast a portion of the module is accessible through the opening in thecarrier. The electrochemical module can have a first insulatingsubstrate carrying a first electrode in communication with the firstconductive area of the carrier, and a second insulating substratecarrying a second electrode in communication with the second conductivearea of the carrier. The first and second electrodes can be facing oneanother in a spaced apart relationship. Alternatively, theelectrochemical module can have an insulating substrate carrying boththe first and second electrodes positioned adjacent to one another onthe same plane. The electrodes can further be offset from one another.The module can also include an electrochemical cavity for receiving afluid sample. The electrochemical cavity can be formed between orcovering the first and second electrodes. The module further includes areagent disposed within the electrochemical cavity and on at least oneof the first and second electrodes for reacting with an analyte of afluid sample received in the electrochemical cavity.

In one embodiment the carrier has a maximum length and maximum widththat is greater than a maximum length and maximum width of theelectrochemical module. While the configuration of the carrier can vary,in certain aspects the carrier can be folded along a fold line to definea top portion carrying the first conductive area and a bottom portioncarrying the second conductive area. The first and second conductiveregions on the carrier can be electrically isolated from one anotheralong the fold line, and optionally between the fold line and theelectrochemical module. The opening in the carrier can be located atvarious locations, for example, along a perimeter of the carrier, andmore particularly along the fold line. The carrier can also include anadhesive disposed between the top and bottom portions of the carrier andconfigured to maintain the top and bottom portions at a fixed distanceapart from one another. Optionally, the adhesive can help to hold theelectrochemical module in place on the carrier.

In other aspects, the electrochemical module can be located on a distalend of the carrier, and a proximal end of the carrier can include firstand second contacts configured to establish an electrical connectionbetween the first and second electrodes and an analyte measurementdevice. The electrochemical module can also include opposed ends mountedon the carrier, and a mid-portion located between the opposed ends andspaced a distance apart from the carrier. In one embodiment, theelectrochemical module has a central portion extending along a centralaxis and containing the electrochemical cavity, and opposed end portionshaving central axes that extend at an angle relative to the central axisof the central portion.

In another embodiment, an electrochemical sensor apparatus is providedthat includes an electrochemical module having an electrochemical cavitywith first and second electrodes, and a sample receiving chamber havinga reagent layer configured to react with an analyte of a fluid samplereceived in the electrochemical cavity. The apparatus also includes acarrier having a top insulating substrate with a first conductiveregion, and a bottom insulating substrate with a second conductiveregion. A distal cut-out extends through a distal end of the top andbottom insulating substrates, and at least a portion of theelectrochemical module extends across the distal cut-out such that thefirst electrode is in electrical communication with the first conductiveregion and the second electrode is in electrical communication with thesecond conductive region. A proximal cut-out extends through a proximalend of the bottom insulating substrate to expose a contact area on thefirst conductive region of the top insulating substrate such that thefirst contact area and a second contact area on the bottom insulatingsubstrate are exposed to allow electrical connection with an analytemeasurement device to establish a connection between the first andsecond electrodes and the analyte measurement device.

In yet another embodiment, an electrochemical module is provided havinga first insulating substrate carrying a first electrode and a secondinsulating substrate carrying a second electrode. The first and secondinsulating substrates can each have opposed sidewalls extending betweenfirst and second terminal ends, and an axis extending between the firstand second terminal ends, and the first and second insulating substratescan be offset from one another such that a first terminal end of thefirst insulating substrate extends a distance beyond a first terminalend of the second insulating substrate to expose the first electrode,and a second terminal end of the second insulating substrate extends adistance beyond a second terminal end of the first insulating substrateto expose the second electrode. The first and second insulatingsubstrates can each have a width extending between the first and secondterminal ends that is at least twice a length extending between theopposed sidewalls. The module can also include at least one spacerdisposed between the first and second insulating substrates andmaintaining the first and second electrodes in a spaced apartrelationship with one another, and an electrochemical cavity formedbetween the first and second electrodes and configured to receive afluid sample. The electrochemical cavity can include a reagentconfigured to react with an analyte of a fluid sample received in theelectrochemical cavity. In one embodiment, the at least one spacer caninclude a first spacer positioned adjacent to the first terminal end ofthe second insulating substrate, and a second spacer positioned adjacentto the second terminal end of the first insulating substrate.

In yet another embodiment, a carrier web is provided having a carrierwith a longitudinally extending fold line defining a top portion havinga first conductive area and a bottom portion having a second conductivearea electrically isolated from the first conductive area, and aplurality of openings spaced a distance apart from one another anddisposed across the fold line. The carrier web also includes a pluralityof electrochemical modules, each module being mounted across one of theplurality of openings, and each electrochemical module having a firstelectrode in communication with the first conductive area of thecarrier, a second electrode isolated from the first electrode and incommunication with the second conductive area of the carrier, and anelectrochemical cavity accessible through the opening in the carrier forreceiving a fluid sample.

In another embodiment, a method for manufacturing an electrochemicalsensing apparatus is provided and includes positioning opposed ends ofan electrochemical module on a carrier such that an electrochemicalcavity formed in the electrochemical module is positioned across anopening formed in the carrier, and folding the carrier to engage theopposed ends of the electrochemical module between top and bottomportions of the carrier. The electrochemical module can include a firstinsulating substrate carrying a first electrode that is positioned inelectrical contact with a first electrically conductive region on thecarrier, and a second insulating substrate carrying a second electrodethat is positioned in electrical contact with a second electricallyconductive region on the carrier. The method can also include, prior topositioning, forming first and second electrically conductive regions onthe carrier such that the first and second electrically conductiveregions are electrically isolated from one another. When the carrier isfolded, the first electrically conductive region can be on the topportion of the carrier and the second electrically conductive region canbe on the bottom portion of the carrier. The method can also include,prior to folding, positioning a spacer on the carrier such that thespacer maintains the top and bottom portions at a distance apart fromone another when the carrier is folded.

BRIEF DESCRIPTION OF THE DRAWINGS

The present disclosure will be more fully understood from the followingdetailed description taken in conjunction with the accompanyingdrawings, in which:

FIG. 1A is a top view of a carrier in an unfolded configuration;

FIG. 1B is a top view of the carrier of FIG. 1A having an adhesive andan electrochemical module (“ECM”) disposed thereon;

FIG. 1C is a top view of the carrier of FIG. 1A having anotherembodiment of an adhesive with an ECM disposed thereon;

FIG. 1D is a perspective view of the carrier and ECM of FIG. 1B, shownin a folded configuration to form a test strip assembly;

FIG. 2A is a side view of the ECM of FIG. 1B;

FIG. 2B is an exploded view of the ECM of FIG. 2A;

FIG. 3A is a perspective view of a carrier web shown in an unfoldedconfiguration and having an adhesive disposed thereon, the carrier webforming multiple carriers for forming multiple test strip assemblies;

FIG. 3B is an enlarged perspective view of a portion of the carrier weband adhesive shown in FIG. 3A;

FIG. 3C is perspective view of the carrier web and adhesive of FIG. 3Ahaving an ECM disposed across each opening in the carrier web;

FIG. 3D is a perspective view of the carrier web, adhesive, and ECMs ofFIG. 3B shown partially folded;

FIG. 4A is a top view of another embodiment of an ECM;

FIG. 4B is a top view shown the ECM of FIG. 4A mounted onto a carrier,shown in a folded configuration, to form another embodiment of a teststrip assembly;

FIG. 5 is a top view of a test strip assembly web, showing multiple teststrip assemblies having a configuration as shown in FIG. 4B;

FIG. 6 is a top view of yet another embodiment of a test strip assemblyhaving multiple ECMs;

FIG. 7 is a top view of one embodiment of an analyte measurement device;and

FIG. 8 is a side view of a strip of electrochemical modules.

DETAILED DESCRIPTION

Certain exemplary embodiments will now be described to provide anoverall understanding of the principles of the structure, function,manufacture, and use of the devices, systems, and methods disclosedherein. One or more examples of these embodiments are illustrated in theaccompanying drawings. Those skilled in the art will understand that thedevices and methods specifically described herein and illustrated in theaccompanying drawings are non-limiting exemplary embodiments and thatthe scope of the present disclosure is defined solely by the claims. Thefeatures illustrated or described in connection with one exemplaryembodiment may be combined with the features of other embodiments. Suchmodifications and variations are intended to be included within thescope of the present disclosure.

The present invention generally provides an electrochemical sensingapparatus having a carrier that supports an electrochemical module, andthat communicates between electrodes on the electrochemical module andan analyte measurement device. The carrier is particularly advantageousas it allows the electrochemical module to have a relatively small size,while providing a large surface area for ease of handling. The smallsize of the electrochemical module can reduce manufacturing costs, asless material is required to form the electrodes. The carrier alsoprovides flexibility in design, allowing for various placement of one ormore electrochemical modules, as well as allowing multiple sensingapparatus to be formed as a unit.

FIGS. 1A-1D illustrate one exemplary embodiment of an electrochemicalsensing apparatus, also referred to herein as a test strip assembly. Asshown, the test strip assembly 10 generally includes a carrier 20, shownin FIG. 1A, and an electrochemical module 30 that is mounted on thecarrier 20, as shown in FIGS. 1B-1D. In general, the carrier 20 hasdimensions that are greater than the module 30, such that the carrier 20serves as a support to facilitate handling of the module 30. A personskilled in the art will appreciate that the test strip assembly 10 canhave various configurations other than those shown, and can include anycombination of features disclosed herein and known in the art. Moreover,each test strip assembly can include any number of electrochemicalmodules at various locations on the carrier for measuring the sameand/or different analytes in a fluid sample.

Carrier

As indicated above, FIG. 1A illustrates one embodiment of a carrier 20.The carrier 20 can have various configurations, but it is typically inthe form of one or more rigid or semi-rigid substrates having sufficientstructural integrity to support the electrochemical module 30 and toallow handling and connection to an analyte measurement device, as willbe discussed in further detail below. The carrier can be formed fromvarious materials, including plastic or cardboard materials. In anexemplary embodiment, materials that do not shed or that exhibitrelatively low shedding of fibers are preferred. The substrate materialtypically is one that is non-conductive. The carrier material can alsohave any thermal coefficient of expansion, including a low thermalcoefficient of expansion, as changes in the volume of the materialduring use will not have any effect on performance. In addition, thecarrier materials can be inert and/or electrochemically non-functional,where they do not readily corrode over time nor chemically react withECM material. The conductive material disposed on the carrier should beresistant to corrosion where the conductivity does not change duringstorage of the strip assemblies.

The shape of the carrier 20 can also vary. In the embodiment shown inFIG. 1A, the carrier 20 has a generally elongate rectangular shape witha length L_(c) that is greater than a width W_(c), the dimensions ofwhich are discussed in further detail below. The carrier 20 includesfirst and second terminal ends 21 a, 21 b, and first and second opposedsidewalls 21 c, 21 d extending between the first and second terminalends 21 a, 21 b. The carrier 20 can be formed from separate top andbottom portions, or as shown the carrier 20 can be configured to befolded along a fold line 22 to define top and bottom portions 20 t, 20 bthat are in facing relationship with one another. A person skilled inthe art will appreciate that the terms “top” and “bottom” as used hereinare intended to serve as a reference for illustration purposes only, andthat the actual position of the portions of the carrier will depend onthe orientation of the carrier. The top and bottom portions 20 t, 20 bof the carrier 20 can allow an electrochemical module, e.g., module 30,to be mounted and engaged therebetween. The location of the fold line 22can vary. In the illustrated embodiment, the fold line 22 is locatedoffset from a mid-line of the carrier 20 to allow one of the top andbottom portions 20 t, 20 b of the carrier, e.g., the bottom portion 20 bin FIG. 1A, to extend a distance beyond the terminal end of the otherportion of the carrier 20, e.g., the top portion 20 t in FIG. 1A. Such aconfiguration facilitates connection to an analyte measurement device,as will be discussed further below. The carrier 20 can also optionallyinclude one or more additional fold lines, which may facilitate spacedapart positioning of the top and bottom portions 20 t, 20 b, as is alsodiscussed further below. The non-conducting substrate of the carrier canbe kiss-cut at the intended fold line in order to facilitate folding. Ifa sharp blade is used to kiss-cut the substrate, sharp edges mayresults, in which case it may be preferable to firmly scribe a groove inthe substrate using a blunt tool. This will push aside the material ofthe substrate into smooth “banks” on either side of the groove in such away that the folded carrier will not have sharp edges.

As further shown in FIG. 1A, the carrier 20 can also include at leastone hole or opening extending therethrough for providing access to theelectrochemical module, as discussed further below. The quantity ofopenings and the location of each opening can vary depending on theintended use, for example, whether more than one module will be presentin a carrier. In the illustrated embodiment, the carrier 20 has a singleopening 24 located symmetrically across the fold line 22. Such aconfiguration will allow the opening 24 to be positioned along aperimeter of the carrier 20 when the carrier 20 is folded, as shown inFIG. 1D. While not shown, the opening 24 can alternatively be positionedalong any edge (e.g., along one of the terminal ends 21 a, 21 b and/orthe opposed sidewalls 21 c, 21 d) of the carrier 20, with correspondingopenings extending through each of the top and bottom portions 20 t, 20b. In other embodiments, the opening can extend through a mid-portion ofthe top and bottom portions 20 t, 20 b of the carrier 20 at a distancespaced apart from the perimeter or outer edge of the carrier 20.

The carrier 20 also includes one or more electrically conducting layersto facilitate communication between electrodes on the electrochemicalmodule, discussed below, and an analyte measurement device. Theelectrically conducting layer(s) can be formed from any conductivematerial, including inexpensive materials, such as aluminum, carbon,grapheme, graphite, silver ink, tin oxide, indium oxide, copper, nickel,chromium and alloys thereof, and combinations thereof. However, preciousmetals that are conductive, such as palladium, platinum, indium tinoxide or gold, can optionally be used. The electrically conductinglayer(s) can be disposed on all or portions of the carrier, but theparticular location(s) of the electrically conducting layer(s) should beconfigured to electrically couple the electrochemical module to theanalyte measurement device. In an exemplary embodiment, the entireportion or a substantial portion of the inwardly facing surface (i.e.,the surface shown in FIG. 1A) of the carrier 20 is coated with theelectrically conducting layer (not shown). As a result, each of the topand bottom portions 20 t, 20 b of the carrier 20 includes anelectrically conducting layer disposed thereon. The carrier 20 can alsoinclude one or more electrical isolation lines, e.g., referred to hereinas “breaks,” formed in the electrically conducting layer to separate thelayer into a first electrically conducting layer and a secondelectrically conducting layer that is isolated from the firstelectrically conducting layer. The break(s) can be formed using varioustechniques known in the art, such as laser etching. If the electricallyconducting layer is formed by printing an ink, then an unprinted areabetween the top and bottom portions 20 t, 20 b will constitute a break.The location of the break(s) can vary. For example, the break(s) canextend along the fold line 22 such that the top portion 20 t includesthe first electrically conducting layer which is electrically isolatedfrom the second electrically conducting layer on the bottom portion 20b. Thus, when the carrier 20 is folded, as shown in FIG. 1D, the firstelectrically conducting layer (not shown) will be positioned on aninwardly facing surface of the top portion 20 t of the carrier 20, andthe second electrically conducting layer (not shown) will be positionedon an inwardly facing surface of the bottom portion 20 b of the carrier20 such that the first and second electrically conducting layers are infacing relationship with one another. As shown in FIG. 1A, theelectrically conducting layer includes a first break formed along thefold line 22, and a second break 26 spaced a distance apart from thefirst break (fold line 22). The breaks can be positioned at variouslocations relative to the fold line 22, including on the same oropposite sides of the fold line 22. A person skilled in the art willappreciate that carrier 20 can be manufactured to include separateelectrically conducting layers, rather than forming a single layer withone or more breaks. The separate layers can be formed from the same ordifferent materials.

In another embodiment, the electrically conducting layers can beconfigured to prevent “auto-starting” of the assays when one or bothsidewalls 21 c, 21 d of the test strip are contaminated, e.g., with asalty solution such as perspiration from a user's fingers. For example,the electrically conducting layers can be formed by printingelectrically conductive inks (e.g., carbon, silver, grapheme, etc.), andthe material can terminate at a distance (e.g., 1 mm) from the sidewalls21 c, 21 d. Such a configuration will prevent contact between theelectrically conducting material and a user's fingers when they graspthe test strip.

The electrically conducting layers can also be configured enable a meterto distinguish between different types of strips (e.g., to measuredifferent analytes in a liquid sample such as glucose, lactate,cholesterol, hemoglobin, etc.). For example, two narrow highlyconducting layers (e.g., printed with silver ink) can extend down fromtabs 12 a, 12 b towards the electrochemical cavity, with a gap betweenthe two narrow highly conducting layers. A layer of less conductingmaterial (e.g., printed with carbon ink) can connect the two narrowhighly conducting layers. When the resistance between the tabs 12 a, 12b is measured, the resistance value will be dominated by the propertiesof the layer of less conducting material. By varying the thickness,width etc. of the layer of less conducting material, it will be possiblefor the meter to distinguish between different types of strips.

In order to maintain electrical separation between the first and secondelectrically conductive areas when the carrier 20 is folded, the carrier20 can further include a spacer layer, which can be an adhesive layer.The spacer layer can function to maintain the top and bottom portions 20t, 20 b of the carrier 20 at a distance apart from one another, therebypreventing electrical contact between the first and second electricallyconducting layers carried by the top and bottom portions 20 t, 20 b. Thespacer layer can also function as a double-sided adhesive to adhere thetop and bottom portions 20 t, 20 b to one another, as well as to securethe electrochemical module 30 to the carrier. The spacer layer can beformed from a variety of materials, including a material with adhesiveproperties, or the spacer layer can include a separate adhesive used toattach the spacer to the carrier and optionally to the electrochemicalmodule. Non-limiting examples of ways in which adhesives can beincorporated into the various test strip assemblies of the presentdisclosure can be found in U.S. patent application Ser. No. 12/570,268of Chatelier et al., entitled “Adhesive Compositions for Use in anImmunosensor” and filed on Sep. 30, 2009, the contents of which isincorporated by reference in its entirety.

The spacer layer can have various shapes and sizes, and it can bepositioned on various portions of the carrier 20. In the embodimentshown in FIG. 1B, a spacer layer 28 is positioned on one side of thefold line 22 and extends over a substantial portion of the inwardlyfacing surface of the bottom portion 20 b of the carrier 20. The spacerlayer 28 can terminate at or just prior to the opening 24, so as toprevent the spacer layer 28 from extending into the opening 24 and fromcontacting the electrochemical module when the carrier 20 is folded.Termination at the opening 24, however, can facilitate the formation ofa seal around the edge of the carrier adjacent to the opening 24. Thespacer layer 28 can also terminate a distance from the second terminalend 21 b of carrier 20 so that, when the carrier is folded as shown inFIG. 1D, the exposed portion of the inwardly facing surface of thebottom portion 20 b is free from any adhesive material.

In another embodiment, shown in FIG. 1C, a spacer layer 29 is likewisepositioned to cover a substantial portion of the inwardly facing surfaceof the bottom portion 20 b. In this embodiment, however, the spacerlayer 29 includes an extension portion 29 a that extends toward or up tothe fold line 22 adjacent to only one of the sidewalls, e.g., the firstsidewall 21 c. In other words, the extension portion 29 a extends alongonly one side of the opening 24. The extension portion 29 a of thespacer layer 29 will thus be positioned between the electrochemicalmodule, e.g., module 30, and the carrier 20 to attach theelectrochemical module 30 to the carrier 20 when the carrier is folded.Preferably, the extension portion 29 a is positioned to contact anexterior surface, e.g., the bottom exterior surface, of theelectrochemical module 30, and not one of the inwardly facing surfacesas will be discussed below. Optionally, the spacer layer 29 can alsoinclude a separate portion 29 b that is positioned on a side of theopening 24 opposite to the extension portion 29 a, and that is alsopositioned on an opposite side of the fold line 22. This separateportion 29 b will thus contact the opposite exterior surface, e.g., thetop exterior surface, of the electrochemical module 30, as will bediscussed below. A person skilled in the art will appreciate that thelocation of the spacer layer can vary.

In other aspects, the spacer layer 29 can be configured to have a sizeand shape that reduces fouling of punching/cutting tools with theadhesive. For example, the edge of the adhesive can be spaced a smalldistance (e.g., 0.5 mm) from the hole 24 to prevent a punch tool used toform the hole from coming into contact with the adhesive. Moreover, ifthe adhesive is printed, the edge of the adhesive can be spaced a smalldistance (e.g., 0.5 mm) from the sidewalls 21 c, 21 d to prevent acutting tool from coming into contact with the adhesive during asingulation step (i.e., when multiple strips are cut to form singularstrips).

The carrier 20 can also include electrical contacts for coupling to ananalyte measurement device. The electrical contacts can be locatedanywhere on the carrier 20. In the illustrated embodiment, the secondterminal end 21 b of the carrier 20 includes first and second contacts12, 14 configured to establish a connection between first and secondelectrodes, respectively, on the module 30 (discussed below) and ananalyte measurement device. As best shown in FIG. 1D, the first contact12 is in the form of first and second tabs 12 a, 12 b located on theterminal end 21 b of the bottom portion 20 b of the carrier 20. When thecarrier is folded, the tabs 12 a, 12 b will extend a distance beyond theterminal end 21 a of the top portion 20 t of the carrier 20, as shown inFIG. 1D. The tabs 12 a, 12 b can be formed by a cut-out or u-shapednotch 16 extending into the second terminal end 21 b of the bottomportion 20 b of the carrier 20 at a substantial mid-portion thereof. Thecut-out 16 is also effective to expose the first electrically conductinglayer on the inwardly facing surface of the top portion 20 t of thecarrier 20, thereby forming the second contact 14 (shown in phantom inFIG. 1D) for connecting the first electrically conducting layer to ananalyte measurement device. A person skilled in the art will appreciatethat the electrical contacts can have a variety of configurations otherthan those illustrated. For example, U.S. Pat. No. 6,379,513, which ishereby incorporated by reference in its entirety, discloses anotherembodiment of an electrochemical cell connection means.

The configuration of the electrically contacts can allow a measurementdevice to recognize a test strip by sensing a decrease in resistancebetween the meter tangs that connect to the tabs 12 a, 12 b on thecarrier, as shown in FIG. 1D. As a further feature, tab 14 in FIG. 1Dcan be made to have a width that allows two additional meter tangs toelectrically connect to the tab 14. This allows the meter to ensure thatsufficient electrical contact is made with tab 14 before the user isprompted to apply a liquid sample to the cavity 42 in theelectrochemical module 30. Such a configuration can prevent a “waitingfor sample” error which can be seen in systems which do not ensure goodelectrical contact prior to initiating an electrochemical assay. Inanother embodiment, where tab 14 does not have a width sufficient toconnect with two meter tags, electrical contact between the meter andtab 14 can still be monitored by performing a “dry capacitance”measurement before the liquid sample is applied to the electrochemicalcavity 42. The capacitance measurement must fall within the rangeexpected for a dry strip before the user is prompted to apply the liquidsample to the cavity 42 in the electrochemical module 30.

The carrier can be configured to couple to a variety of analytemeasurement devices having various configurations. In general, themeasurement device can include a processor, which may include one ormore control units configured for performing calculations capable ofcalculating a correction factor in view of at least one measured orcalculated parameter as well as configured for data sorting and/orstorage. The microprocessor can be in the form of a mixed signalmicroprocessor (MSP) such as, for example, a member of the TexasInstruments MSP 430 family. In addition, the microprocessor can includevolatile and non-volatile memory. In another embodiment, many of theelectronic components can be integrated with the microcontroller in theform of an application specific integrated circuit.

The dimensions of the carrier can vary significantly depending on theconfiguration of the analyte measurement device, as well as the quantityand configuration of the electrochemical module(s) on the test stripassembly. In the embodiment shown in FIG. 1A, and by way of non-limitingexample, the carrier 20 can have a width W_(c) that is in the range ofabout 0 mm to 4 mm larger than the width of the electrochemical module.For example, the width W_(c) of the carrier 20 can be in the range ofabout 5 mm to 50 mm. Also by way of non-limiting example, the carrier 20can have a length L_(c) in the unfolded configuration that is in therange of about 20 mm to 200 mm, and more preferably 30 mm to 50 mm. Thedimensions of the opening(s) in the carrier 20 can also vary, but in anexemplary embodiment the opening 24 has a generally oval or rectangularconfiguration with a width W_(o) as measured in a direction extendingbetween the opposed sidewalls 21 c, 21 d that is in the range of about 3mm to 49 mm. The length L_(o) (in the unfolded configuration) of theopening can be in the range of about 0 to 6 mm larger than twice thelength of the electrochemical module (the factor of two is requiredsince the carrier web will be folded). For example, the length L_(o) ofthe opening can be in the range of about 3 to 30 mm. When the carrier 20is folded as shown in FIG. 1D, the opening 24 will have a depth D_(o)that is one half of the length L_(o), as measured from the fold line 22inward. A person skilled in the art will appreciate that the terms“about” and “approximately” as used herein for any numerical values orranges indicate a suitable dimensional tolerance that allows the part orcollection of components to function for its intended purpose asdescribed herein.

Electrochemical Module

The electrochemical module (ECM) can also have a variety ofconfigurations and various electrochemical cell sensors known in the artcan be used. In one embodiment, the module can include multipleelectrodes and a reagent layer, and the module can be configured toreceive and react with an analyte in a fluid sample. The multipleelectrodes can be configured in any suitable configuration, such asadjacent one another and in the same plane, or facing one another in anopposed spaced apart relationship. The module can be mounted onto acarrier, such as carrier 20, such that the carrier serves as a supportfor the module and facilitates handling. As indicated above, the carriercan also electrically couple the module to an analyte measurementdevice.

While the module can have various configurations, in the embodimentshown in FIGS. 2A-2B, the electrochemical module 30 generally includes afirst insulating layer 32 carrying a first electrode 36, a secondinsulating layer 34 carrying a second electrode 38 that is in facingrelationship with the first electrode 36 on the first insulating layer32, and one or more spacers 40 a, 40 b maintaining the first and secondelectrodes 36, 38 at a distance apart from one another to define acavity or chamber 42 therebetween for receiving a fluid analyte. Forease of reference, the first insulating layer 32 is also referred toherein as the top insulating layer, and the second insulating layer 34is also referred to as the bottom insulating layer. The terms “top” and“bottom” are merely used to describe the illustrated orientation and arenot intended to limit the layers to a particular orientation. Theillustrated electrochemical module 30 can also include a reagent 44disposed on one of the first and second electrodes, e.g., the secondelectrode 38, and disposed between the spacers 40 a, 40 b and within thechamber 42 for reacting with an analyte. A person skilled in the artwill appreciate that the electrochemical module 30 can have a variety ofconfigurations, including having other electrode configurations, such asco-planar electrodes.

The first and second insulating layers 32, 34 can each have variousshapes and sizes, and the particular configuration of the insulatinglayers 32, 34 can vary depending on the particular configuration of thecarrier 20. In the illustrated embodiment, the first and secondinsulating layers 32, 34 each have a generally rectangular shape. Theinsulating layers 32, 34 can be formed from various materials, but in anexemplary embodiment the insulating layers 32, 34 are formed from amaterial having a small coefficient of thermal expansion such that theinsulating layers 32, 34 do not adversely affect the volume of thereaction chamber 42, as will be discussed in detail below. In oneexemplary embodiment, at least one of the insulating layers, e.g., thefirst layer 32, can be formed from a transparent material to allowvisualization of fluid flow into the reaction chamber. Suitablematerials include, by way of non-limiting example, plastics (such asPET, PETG, polyimide, polycarbonate, polystyrene), ceramic, glass,adhesives.

As indicated above, each insulating layer 32, 34 can carry an electrode36, 38. As shown in FIG. 2A, an inwardly facing surface of the firstinsulating layer 32 carries the first electrode 36, and an opposinginwardly facing surface of the second insulating layer 34 carries thesecond electrode 38. The electrodes 36, 38 can each be formed from alayer of conductive material, such as gold, palladium, carbon, silver,platinum, tin oxide, iridium, indium, and combinations thereof (e.g.,indium doped tin oxide). Carbon in the form of graphene may also beused. The conductive material can be deposited onto the insulatinglayers 32, 34 by various processes, such as sputtering, electrolessplating, thermal evaporation and screen printing. In an exemplaryembodiment, the reagent-free electrode, e.g., the first electrode 36, isa sputtered gold electrode, and the electrode containing the reagent 44,e.g., the second electrode 38, is a sputtered palladium electrode. Asdiscussed in further detail below, in use one of the electrodes canfunction as a working electrode and the other electrode can function asthe counter/reference electrode.

When the electrochemical module 30 is assembled, the first and secondinsulating layers 32, 34, and thus the first and second electrodes 36,38, can be held together at a spaced distance apart by one or morespacers. As shown in FIG. 2B, the electrochemical module 30 includesfirst and second spacers 40 a, 40 b, also referred to as adhesives. Theillustrated spacers 40 a, 40 b each have a generally rectangularconfiguration with a length L_(s) that can be substantially equal to alength L_(i) of the insulating layers 32, 34, and a width W_(s) that issignificantly less than a width W, of the insulating layers 32, 34.However, the shape and size, as well as the quantity, of the spacers 40a, 40 b can vary significantly. As shown, the first spacer 40 a ispositioned adjacent to a first terminal end 34 a of the second/bottominsulating layer 34, and the second spacer 40 b is positioned near amid-portion of the second/bottom insulating layer 34 such that a spaceor gap is defined between the first and second spacers 40 a, 40 b. Thesecond terminal end 32 b of the first/top insulating layer 32 can bepositioned in substantial alignment with an edge of the second spacer 40b farthest from the first spacer 40 a, such that the first terminal end32 a of the first/top insulating layer 32 extends a distance beyond thefirst terminal end 34 a of the second/bottom insulating layer 34. As aresult, the second terminal end 34 b of the second/bottom insulatinglayer 34 will extend a distance D_(i) beyond the second terminal end 32b of the first/top insulating layer 32, as shown in FIG. 2A. The firstand second insulating layers 32, 34 can thus be positioned offset fromone another, thereby exposing an inwardly facing portion of each of thefirst and second electrodes 36, 38. A person skilled in the art willappreciate that the particular configuration, including the shape,orientation, and location of the spacer(s) and the insulating layersrelative to one another can vary.

As indicated above, the spacers 40 a, 40 b and electrodes 36, 38 definea space or gap, also referred to as a window, therebetween which formsan electrochemical cavity or reaction chamber 42 for receiving a fluidsample. In particular, the first and second electrodes 36, 38 define thetop and bottom of the reaction chamber 42, and the spacers 40 a, 40 bdefine the sides of the reaction chamber 42. The gap between the spacers40 a, 40 b will result in the opposed sidewalls of the module 30 havingopenings or inlets extending into the reaction chamber 42. The fluidsample can thus be loaded through the side openings.

As further shown in FIG. 2A, the reaction chamber 42 can also include areagent 44 disposed on at least one of the electrodes, e.g., the secondelectrode 38. Alternatively, the reagent layer can be disposed onmultiple faces of the reaction chamber 42. The reagent 44 can be formedfrom various materials, including various mediators and/or enzymes.Suitable mediators include, by way of non-limiting example,ferricyanide, ferrocene, ferrocene derivatives, osmium bipyridylcomplexes, and quinone derivatives. Suitable enzymes include, by way ofnon-limiting example, glucose oxidase, glucose dehydrogenase (GDH) basedon pyrroloquinoline quinone (PQQ) co-factor, GDH based on nicotinamideadenine dinucleotide co-factor, and FAD-based GDH [E.C.1.1.99.10]. Oneexemplary reagent formulation, which would be suitable for making thereagent 44, is described in pending U.S. Pat. No. 7,291,256, entitled“Method of Manufacturing a Sterilized and Calibrated Biosensor-BasedMedical Device,” the entirety of which is hereby incorporated herein byreference. The reagent 44 can be formed using various processes, such asslot coating, dispensing from the end of a tube, ink jetting, and screenprinting. Such processes are described, for example, in the followingU.S. Patents, which are hereby incorporated by reference in theirentireties: U.S. Pat. Nos. 6,749,887; 6,869,441; 6,676,995; and6,830,934. While not discussed in detail, a person skilled in the artwill also appreciate that the various electrochemical modules disclosedherein can also contain a buffer, a wetting agent, and/or a stabilizerfor the biochemical component.

The size of the electrochemical module 30 and its components can vary.For example, in one embodiment, the first and second insulating layers32, 34 can each have substantially the same size, with a length L_(i)and width W_(i) that is less than a length L_(c) and width W_(c) of thecarrier 20. By way of non-limiting example, the insulating layers 32, 34can each have a width W_(i) that is at least twice the length L_(i). Forexample, the width W_(i) can be in the range of about 3 mm to 48 mm, andmore preferably about 6 mm to 10 mm, and a length L_(i) in the range ofabout 0.5 mm to 20 mm, and more preferably 1 mm to 4 mm. The distanceD_(e) between the top electrode 36 and the bottom electrode 38, as wellas the dimensions of the spacers 40 a, 40 b, can also vary depending onthe desired volume of the reaction chamber 42. In an exemplaryembodiment, the reaction chamber 42 has a small volume. For example, thevolume can range from about 0.1 microliters to about 5 microliters,preferably about 0.2 microliters to about 3 microliters, and morepreferably about 0.2 microliters to about 0.4 microliter. To provide thesmall volume, the gap between the spacers 40 a, 40 b can have an arearanging from about 0.005 cm² to about 0.2 cm², preferably about 0.0075cm² to about 0.15 cm², and more preferably about 0.01 cm² to about 0.08cm², and the thickness of the spacers 40 a, 40 b (i.e., the heightH_(s)) can range from about 1 micron to 500 microns, and more preferablyabout 10 microns to 400 microns, and more preferably about 40 micros to200 micros, and even more preferably about 50 microns to 150 microns. Aswill be appreciated by those skilled in the art, the volume of thereaction chamber 42, the area of the gap between the spacers 40 a, 40 b,and the distance between the electrodes 36, 38 can vary significantly.

Test Strip Assembly

Various techniques can be used to prepare a test strip assembly havingboth a carrier and an electrochemical module. Referring back to FIGS.1A-1D, in one embodiment a single test strip assembly 10 can be formedby providing a carrier, e.g., carrier 20, and placing a spacer layer 28or 29 and an electrochemical module 30 onto the carrier 20. Theelectrochemical module 30 is preferably mounted onto the carrier 20 insuch a way as to allow the carrier 20 to function as a support forhandling the apparatus, while also allowing easy access to the reactionchamber 42. While the particular location of the module 30 relative tothe carrier 20 can vary depending on the configuration of the module 30,the quantity of modules 30 mounted onto the carrier 20, and theconfiguration of the carrier 20, in the illustrated embodiment themodule 30 is mounted on the carrier 20 such that the module 30 extendsacross the opening 24 and is positioned along or adjacent to one side ofthe fold line 22. The opposed terminal ends of the module 30 are thus incontact with the carrier 20, while a central or mid-portion of themodule 30 is not in contact with and is spaced apart from the carrier20. The spacer layer 28 or 29 can likewise be positioned at variouslocations on the carrier 20. As explained above, the spacer layer 28 or29 can function as an adhesive to secure the module 30 between the topand bottom portions 20 t, 20 b of the carrier 20, thus preventingmovement of the module 30 relative to the carrier 20. While FIG. 1Billustrates the spacer 28 positioned a distance apart from the module 30such that the spacer 28 does not contact the module 30 even when thecarrier 20 is folded, the spacer can have other configurations such asthe configuration shown in FIG. 1C in which the spacer 29 has portions29 a, 29 b that extend over at least the terminal end portions of themodule 30 to adhere the module 30 directly to the carrier 20.

Once the module 30 and spacer 28 or 29 are positioned on the carrier 20,the carrier 20 can be folded along the fold line 22, as shown in FIG.1D, thereby adhering the top and bottom portions 20 t, 20 b to oneanother and thereby engaging the electrochemical module 30 between thetop and bottom portions 20 t, 20 b. When folded, the carrier 20 willhave a proximal end 20p with the first and second electrical contacts12, 14, and a distal end 20 d having the module 30 located thereon. Themodule 30 can be positioned adjacent to or along the terminal distaledge or perimeter of the carrier 20 such that one side of the openingextending into the reaction chamber 42 is positioned along the perimeterto allow for side loading of a fluid sample into the reaction chamber42. The other side of the module 30, e.g., the proximal side, is spaceda distance apart from the inner edge of the opening 24 to create a gap.The gap between the carrier and the module allows a fluid sample to flowinto the reaction chamber 42 without flowing into the carrier 20, e.g.,between the top and bottom portions 20 t, 20 b. As used herein, the term“proximal” indicates that a reference structure is close to the testmeter and the term “distal” indicates that a reference structure isfarther away from the test meter.

When fully assembled, as shown in FIG. 1D, the inwardly facing surfaceof the top electrode 36 will directly contact and electrically connectwith the inwardly facing surface of the bottom portion 20 b of thecarrier 20, and the inwardly facing surface of the bottom electrode 38will directly contact and electrically connect with the inwardly facingsurface of the top portion 20 t of the carrier 20. The connectionresults from the offset configuration of the insulating layers 32, 34and electrodes 36, 38, as shown in FIG. 2A. In particular, FIG. 2B showsthat the connection will occur at the first terminal end 32 a of thefirst/top insulating layer 32 that extends a distance beyond the firstterminal end 34 a of the second/bottom insulating layer 34, and at thesecond terminal end 34 b of the second/bottom insulating layer 34 thatextends a distance beyond the second terminal end 32 b of the first/topinsulating layer 32. The first electrode 36 is shielded from contactingthe top portion 20 t of the carrier 20 by the first insulating layer 32,and the second electrode 38 is shielded from contacting the bottomportion 20 b of the carrier by the second insulating layer 34. The firstelectrode 36 will therefore communicate with an analyte measurementdevice through the bottom portion 20 b of the carrier and through thefirst electrical contact 12, e.g., tabs 12 a and 12 b, and the secondelectrode 38 will communicate with the analyte measurement devicethrough the top portion 20 t of the carrier and through the secondelectrical contact 14. The spacer layer will maintain electricalseparation between the top and bottom portions 20 t, 20 b of the carrier20.

The assembled dimensions of the ECM and the test strip assembly canvary, but in one exemplary embodiment the ECM has a width of about 10 mmand a length (measured in a proximal-distal direction) of about 2 mm,and the carrier or test strip assembly has a width of about 12 mm and alength (measured proximal-distal direction) of about 40 mm. Thedimensions of the carrier are thus significantly larger than thedimensions of the ECM.

Exemplary Manufacturing Process

In one exemplary embodiment, a test strip assembly can be manufacturedby applying a coating of conducting carbon ink to a 76 mm wide web ofglossy cardboard, PET or polypropylene having an appropriate stiffness.The thickness of the coating should be sufficient to reduce the surfaceresistance such that the overall resistance of the connector track isless than 200 Ohms. The conducting layer on the carrier can be etcheddownweb with a laser or a mechanical scriber at a location 40 mm fromone edge such that the web is divided into two electrically isolatedfunctional regions, e.g., top portion 20 t and bottom portion 20 b. Fora carrier web having multiple test strip assemblies, e.g., a multi-paneltest strip assembly, the web can also be etched in a crossweb directionat 20 mm intervals to separate each test strip assembly. A spacer oradhesive layer, e.g., spacer 128, covered by a release liner can belaminated to the web, as shown in FIG. 3C, such that one of its edges is4 mm from the terminal end of the bottom portion 20 b of the carrier weband the other edge is about 5 mm above the center line of the carrierweb. Referring back to FIG. 3C, note that the center line can correspondto the location of the fold line 122. Holes 124, having a diameter of 8mm, can be punched into the carrier web in a downweb direction along theetched line at 12 mm intervals (center-to-center), and slots can bepunched in the bottom (proximal) end. For a multi-panel test stripassembly, the holes can be in the middle of each 20 mm section. A 34 mmwide track of double-sided adhesive separator (about 95±2 micrometersheight with 50 micrometer release liners) can be kiss-cut and the wasteremoved in such a way that there are 4 repeating patterns, shown in partin FIG. 8, which consist of (1) a 1.2 mm wide cavity (labeled “a” inFIG. 8) in the middle that will form an electrochemical cavity in alater step, and (2) a 2.4 mm wide spacer section separator (labeled “b”in FIG. 8) on each side that will form the walls of the electrochemicalcavity in a further step. The term kiss-cut can be used when referringto a partial cut through a laminate structure. For example, the laminatestructure including an Au-PET layer, an adhesive spacer layer, and aPd-PET layer can be kiss-cut such that only the Au-PET layer or Pd-PETlayer is cut. The remaining separator will form a reagent-free cavity (2mm on each side, labeled “c” in FIG. 8) that will expose overhangingelectrodes in a further step. A 32 mm wide track of PET filled withbarium sulfate particles is sputtered with 60 nm of Pd, brought intocontact with 0.3 mM MESA in water for 20 seconds, and then the excessliquid is blown off with an air knife. Four strips of reagent (identicalor different) are applied to the Pd electrode, 8 mm apart(center-to-center). The double-sided adhesive separator is bonded to thePd electrode in such a way that each 1.2 mm wide cavity overlays areagent stripe. A 32 mm wide track of clear PET is sputtered with 30 nmof Au, brought into contact with 0.3 mM MESA in water for 20 seconds,and then the excess liquid is blown off with an air knife. ThePd-separator-Au tri-laminate is kiss-cut through the electrode layeronly from two directions, as shown by the arrows in FIG. 8, in such away that either the Pd or the Au extends past the edge of the spacerlayer and the other electrode layer. The different tracks oftri-laminate can be separated to form four electrochemical modules, twoof which are shown in FIG. 8 and labeled A and B, with only a portion ofthe remaining two being shown. The total width of each of the moduleswill be 2 mm (section c, upper electrode) +2.4 mm (section b,trilaminate) +1.2 mm (section a, cavity plus reagent) +2.4 mm (sectionb, trilaminate) +2 mm (section c, lower electrode), for a total of 10mm. This is larger than the total length of 32 divided by 4 (about 8 mm)because of the separate exposed regions of upper and lower electrodes.Each module of tri-laminate is cut into 2 mm long sensors and placed onthe carrier as described above. One way to achieve this is to push aleading edge of the tri-laminate into a slot on a wheel and cut off the2 mm wide sensor. The wheel would then rotate so that another slot wouldreceive the leading edge of the tri-laminate web and another piece of 2mm wide sensor would be cut off, etc. The carrier web would advance pastthe opposite end of the wheel and receive each 2 mm wide sensor in sucha way that the appropriate edge of the electrochemical cavity coincideswith the middle of a hole in the carrier. For the multi-analyte teststrip assembly, the track order along the carrier would be 1-2-3-4,1-2-3-4, etc., with a separate rotating wheel for each reagent. Sinceeach small ECM is 10 mm wide and each carrier is 12 mm wide, there willbe sufficient gap between each edge of the ECM and carrier so that thecutting machine does not disturb the ECM in the final “singulation”step. The carrier is folded at a line which was laser etched downweb,bonded to the double sided adhesive separator, optionally printed with alogo and other required information, and then chopped as appropriate.The folding process can either be done continuously in a web process, orthe web can be chopped into cards which can then be folded. For themulti-analyte test strip assembly, a set of four ECMs can be choppedinto a single card. If all reagents are identical and an average valueis required, then each card can contain two or four ECMs. Alternatively,the web can be processed for the simplest application with single,identical sensors.

Other Embodiments

While one embodiment of a test strip assembly 10 is shown in FIG. 1D,FIGS. 3A-4 provides various other embodiments of test strip assemblies.A person skilled in the art will appreciate that, while not specificallydiscussed, the test strip assemblies set forth in FIGS. 3A-4 can includeany combination of features discussed above with respect to FIGS. 1A-1Dand/or other features known in the art.

In one embodiment, a carrier web having multiple test strips assembliescan be formed. Such a configuration allows for mass production ofmultiple test strip assemblies. Each test strip assembly can simply becut or otherwise removed from the carrier web prior to use. For example,the carrier web can include scored regions between each test stripassembly to facilitate removal of a test strip assembly without the needfor scissors or another cutting mechanism. Alternatively, an analytemeasurement device can have multiple terminals configured to accept acarrier web having multiple electrochemical modules. Such aconfiguration could allow for multiple analytes to be testedsimultaneously. Such a configuration could, in other embodiments, allowmultiple readings of a single analyte to be taken, thus allowing thedevice to exclude outliers and display an average. This would provide arobust estimate of the analyte concentration and can enhance both theprecision and the accuracy of the measurement.

While the carrier web can have various configurations, FIG. 3Aillustrates one embodiment of a carrier web 100 having a generallyelongate rectangular configuration. The carrier web 100 can have thesame length L_(w) as the length L_(c) of the carrier 20 discussed abovewith respect to FIG. 1A, however the width W_(w) of the carrier web 100can be multiple times the width W_(c) of the carrier 20 discussed withrespect to FIG. 1A. In particular, the width W_(w) of the carrier web100 preferably corresponds to the width W_(c) of the carrier of FIG. 1Atimes the number of carriers that the carrier web 100 is to contain. Forexample, if the carrier web 100 is configured to produce ten (10)carriers, and thus ten test strip assemblies, then the width W_(w) ofthe carrier web 100 will be about ten (10) times the width W_(c) of asingle carrier. A person skilled in the art will appreciate that theparticular dimensions of the carrier web 100 can vary.

As further shown in FIGS. 3A and 3B, the carrier web 100 can includemultiple openings 124 formed therein, each opening 124 having aconfiguration similar to the openings 24 previously discussed above withrespect to FIG. 1A. As shown, the openings 124 can be spaced a distanceapart from one another and longitudinally aligned along an intended foldline 122 on the carrier web 100. The carrier web 100 can also include anadhesive or spacer 128 disposed on various portions of the carrier web100. In the illustrated embodiment, the spacer 128 is positioned on oneside of the intended fold line 122. The spacer 128 can include a portion128 a that extends along one side of each opening 124 for contacting abottom surface of the electrochemical module, e.g., module 130, whenmounted thereon. The spacer 128 can also include a separate, secondportion 128 b that is positioned on an opposite side of each opening124, and on an opposite side of the fold line 122 such that the secondportion 128 b of spacer 128 contacts a top surface of theelectrochemical module 130. When the carrier web 100 is folded, thespacer 128 will connect the top and bottom portions of the carrier web100 to one another, while maintaining the top and bottom portions 100 t,100 b at a spaced apart distance from one another. The portions ofspacer 128 that extend along each side of the openings 124 will adhereto and affix each electrochemical module 130 to the carrier web 100,thereby maintaining the modules 130 in a fixed position relative to thecarrier web 100. p FIG. 3C illustrates the carrier web 100 of FIGS. 3Aand 3B having an electrochemical module 130 mounted to extend acrosseach opening 124 in the web. Each module 130 on the web 100 can have aconfiguration as previously explained. In other embodiments, the modules130 on the carrier web 100 can differ from one another, e.g., to allowdifferent analytes to be tested. A person skilled in the art willappreciate that the configuration of the carrier web 100 and modules 130mounted thereon, as well as the location of each module 130 on thecarrier web 100, can vary significantly depending on the intended use.

FIG. 4A illustrates another embodiment of an electrochemical module 230,and FIG. 4B illustrates the electrochemical module mounted 230 onto acarrier 220 to form a test strip assembly 200. In this embodiment, theelectrochemical module 230 has a curved or bent configuration toposition the electrochemical cell or reaction chamber 242 a fartherdistance apart from the inner edge of the opening 224 in the carrier220. In particular, the electrochemical module 230 has a configurationsimilar to that described above with respect to FIGS. 2A and 2B, howeverthe module 230 includes bent or angled end portions. As shown, a portionof the module 230 which contains the reaction chamber 242, e.g., amid-portion 230 a, extends along a central axis L₁, and two terminal endportions 230 b, 230 c each extend along axes L₂, L₃ that extend at anangle a relative to the central axis L₁ of the mid-portion 230 a. Thecentral axis L₁ can also extend orthogonal to a direction of flow of asample into the reaction chamber 242. The angle a between each endportion 230 b, 230 c and the mid-portion 230 a can vary. For example, inthe illustrated embodiment the angle a is an acute angle, and moreparticularly is greater than 0 degrees and less than 90 degrees. Forexample, the angle α can be about 45 degrees. Each terminal end portion230 b, 230 c is preferably oriented to extend away from the central axisL₁ of the mid-portion 230 a in the same direction. Such a configurationallows the terminal end portions 230 b, 230 c to be mounted onto thecarrier 220 on opposed sides of the opening 242, as shown in FIG. 4B,with the mid-portion 230 a positioned a distance apart from the inneredge of the opening 224. The distance d can vary depending on the lengthof the end portions 230 b, 230 c, but in an exemplary embodiment theelectrochemical module 230 is configured such that the distal-most edge230 d of the module 230 is positioned distal to the distal-most edge 220d of the carrier 220. As a result, the distance d between the proximaledge of the module 230 and the proximal inner edge of the carrier 220 atthe opening 224 is increased to help prevent fluid from flowing from thereaction chamber 242 into the carrier 220.

FIG. 5 illustrates multiple electrochemical modules 230, having the sameconfiguration as the module of FIG. 4A, mounted onto a carrier web 300,similar to the carrier web 100 discussed above with respect to FIG. 3D.A person skilled in the art will appreciate that the web and the modulescan have a variety of configurations, and can include any combination offeatures disclosed herein and/or known in the art.

FIG. 6 illustrates another embodiment of a test strip assembly 400,shown fully assembled in a folded configuration. In this embodiment, theassembly 400 includes multiple electrochemical modules 430 a, 430 b, 430c mounted at various locations on a single carrier 420. In particular,the carrier 420 has a configuration similar to the carrier 20 of FIG.1A, however, in addition to the distal opening 424 b, the carrier 420includes first and second opposed side openings 424 a, 424 c extendingthrough each of the top and bottom portions of the carrier 420. Thisallows three electrochemical modules 430 a, 430 b, 430 c to be mountedonto the carrier 420 between the top and bottoms portions of the carrier420. Each module 430 a, 430 b, 430 c can be positioned to extend acrossan opening 424 a, 424 b, 424 c, as shown. Each module 430 a, 430 b, 430c can be configured to measure the same analyte in a fluid sample, or tomeasure different analytes. Multiple electrical isolation lines or“breaks” 426 can be formed in the carrier to electrically isolate eachmodule 430 a, 430 b, 430 c and allow the carrier 420 to provide separateelectrically connections between each module 430 a, 430 b, 430 c anddifferent electrical connections on an analyte measurement device. Aperson skilled in the art will appreciate that each module can havevarious configurations, including a configuration similar to theembodiment of FIG. 4A, and that the modules can be mounted at variouslocations on the carrier 420, or on a carrier web. The electricalcontacts for coupling to an analyte measurement device can also have avariety of configurations.

Use

The test strip assemblies disclosed herein are suitable for use in thedetermination of a wide variety of analytes in a wide variety ofsamples, and are particularly suited for use in the determination ofanalytes in whole blood, plasma, serum, interstitial fluid, orderivatives thereof. By way of non-limiting example, the electrochemicalmodules can be configured as a glucose sensor, a lactate sensor based onlactate dehydrogenase, a lactate dehydrogenase sensor which includeslactate (to report on tissue damage), a ketone body sensor based onβ-hydroxy-butyrate dehydrogenase, a cholesterol sensor based oncholesterol oxidase, a hemoglobin sensor which includes a cytolyticagent such as deoxycholate, and an immunosensor which contains anantibody and/or an antigen.

In use, a test strip assembly can be loaded into an analyte measurementdevice, such as a meter. An audible confirmation of connection canoptionally be provided. The test meter will connect to the first andsecond electrical connections on the test strip assembly to form acomplete circuit. An example is shown in FIG. 1D where contacts 12 a and12 b can be used to recognize strip insertion into the meter. The testmeter can measure the resistance or electrical continuity between theelectrical contacts on the test strip assembly to determine whether thetest strip is electrically connected to the test meter. The test metercan use a variety of sensors and circuits to determine when a test stripis properly positioned with respect to the test meter. In oneembodiment, a circuit disposed in the test meter can apply a testpotential and/or a current between first electrical contact and secondelectrical contact. Once the test meter recognizes that a test stripassembly has been inserted, the test meter turns on and initiates afluid detection mode. In one embodiment, the fluid detection mode causesthe test meter to apply a constant current of about 1 microamperebetween the first electrode and the second electrode. An example isshown in FIG. 1D where the flow of current between contact 14 andcontact 12 can be used to detect fluid in the strip. Because the teststrip assembly is initially dry, the test meter measures a maximumvoltage, which is limited by the hardware within the test meter. Thefluid sample, such as a physiological fluid or control solution, can bedelivered to the sample reaction chamber 42 for electrochemical analysisvia the opening until the fluid sample fills the sample reactionchamber. When the fluid sample bridges the gap between the first andsecond electrodes, the test meter will measure a decrease in measuredvoltage (e.g., as described in U.S. Pat. No. 6,193,873, the entirety ofwhich is hereby incorporated by reference), which is below apredetermined threshold causing the test meter to automatically initiatethe analyte test, e.g., a glucose test.

It should be noted that the measured voltage may decrease below apre-determined threshold when only a fraction of the sample reactionchamber has been filled. A method of automatically recognizing that afluid was applied does not necessarily indicate that the sample reactionchamber has been completely filled, but can only confirm a presence ofsome amount of fluid in the sample reaction chamber. Once the test meterdetermines that a fluid has been applied to the test strip assembly, ashort, but non-zero amount of time may still be required to allow thefluid to completely fill the sample reaction chamber. At this point, themeter can apply a series of electrical potentials, measure theelectrical current versus time, and use an algorithm to calculate theconcentration of analyte in the test liquid.

By way of non-limiting example, FIG. 7 illustrates one embodiment of ananalyte measurement device, e.g., a diabetes management unit (DMU) 500.The DMU 500 generally includes a housing 502, user interface buttons504, a display 506, and a test strip port opening 508. The userinterface buttons 504 can be configured to allow the entry of data,navigation of menus, and execution of commands. Data can include valuesrepresentative of analyte concentration, and/or information, which arerelated to the everyday lifestyle of an individual. Information, whichis related to the everyday lifestyle, can include food intake,medication use, occurrence of health check-ups, and general healthcondition and exercise levels of an individual. The DMU can also becombined with an insulin delivery device, an additional analyte testingdevice, and/or a drug delivery device. The DMU may be connected to acomputer or server via a cable or a suitable wireless technology suchas, for example, GSM, CDMA, BlueTooth, WiFi and the like. A personskilled in the art will appreciate that the analyte measurement devicecan have a variety of configurations, and that various devices known inthe art can be used. By way of non-limiting example, one exemplaryembodiment of an analyte measurement device is disclosed in U.S.Publication No. 2009/0084687 entitled “Systems and Methods ofDiscriminating Control Solution From A Physiological Sample,” which ishereby incorporated by reference in its entirety.

One skilled in the art will appreciate further features and advantagesof the present disclosure based on the above-described embodiments.Accordingly, the present disclosure is not to be limited by what hasbeen particularly shown and described, except as indicated by theappended claims. All publications and references cited herein areexpressly incorporated herein by reference in their entirety.

1. An electrochemical sensing apparatus, comprising: a carrier havingfirst and second electrically conductive regions that are electricallyisolated from one another, the carrier including an opening extendingtherethrough; and an electrochemical module mounted to the carrier suchthat at least a portion of the electrochemical module extends across theopening, the electrochemical module having an electrochemical cavitywith a first electrode in electrical communication with the firstconductive region of the carrier, a second electrode in electricalcommunication with the second conductive region of the carrier, and asample receiving chamber that includes a reagent layer.
 2. The apparatusof claim 1, wherein the carrier is folded along a fold line to define atop portion and a bottom portion.
 3. The apparatus of claim 2, whereinthe opening extends across the fold line.
 4. The apparatus of claim 1,wherein the electrochemical module has a maximum length and a maximumwidth that is less than a maximum length and a maximum width of thecarrier.
 5. The apparatus of claim 1, wherein the carrier has a topportion carrying the first conductive region and a bottom portioncarrying the second conductive region, and wherein the electrochemicalmodule is mounted between the top and bottom portions.
 6. The apparatusof claim 5, further comprising an adhesive disposed between the top andbottom portions of the carrier and configured to maintain the top andbottom portions at a fixed distance apart from one another.
 7. Theapparatus of claim 1, wherein the electrochemical module has opposedends engaged between the top and bottom portions of the carrier, andwherein the sample receiving chamber is located between the opposed endsis spaced a distance apart from the carrier.
 8. The apparatus of claim1, wherein the opening is located on a distal end of the carrier, and aproximal end of the carrier includes first and second contactsconfigured to establish a connection between the first and secondelectrodes and an analyte measurement device.
 9. The apparatus of claim1, wherein the electrochemical module includes: a top insulatingsubstrate carrying the first electrode; a bottom insulating substratecarrying the second electrode; and a spacer disposed between the firstand second electrodes and maintaining the first and second electrodes ina spaced apart relationship with one another.
 10. The apparatus of claim9, wherein the top and bottom insulating substrates are offset from oneanother such that a portion of the first electrode on the top insulatingsubstrate is in contact with the second electrically conductive regionon the carrier, and a portion of the second electrode on the bottominsulating substrate is in contact with the first electricallyconductive region on the carrier.
 11. The apparatus of claim 1, whereinthe electrochemical module has a central portion extending along acentral axis and containing the electrochemical cavity, and opposed endportions having central axes that extend at an angle relative to thecentral axis of the central portion.
 12. The apparatus of claim 1,wherein the carrier is inert.
 13. An electrochemical sensing apparatus,comprising: a carrier having a first conductive area, a secondconductive area electrically isolated from the first conductive area,and an opening formed through the carrier; and an electrochemical modulemounted on the carrier such that at least a portion of the module isaccessible through the opening in the carrier, the electrochemicalmodule having a first electrode in communication with the firstconductive area of the carrier, a second electrode in communication withthe second conductive area of the carrier, an electrochemical cavity forreceiving a fluid sample, the electrochemical cavity being formedbetween the first and second electrodes, and a reagent disposed withinthe electrochemical cavity on at least one of the first and secondelectrodes for reacting with an analyte of a fluid sample received inthe electrochemical cavity.
 14. The apparatus of claim 13, wherein theelectrochemical module has a first insulating substrate carrying thefirst electrode, and a second insulating substrate carrying the secondelectrode, the first and second electrodes facing one another in aspaced apart relationship
 15. The apparatus of claim 13, wherein theopening is located along a perimeter of the carrier.
 16. The apparatusof claim 13, wherein the carrier has a maximum length and maximum widththat is greater than a maximum length and maximum width of theelectrochemical module.
 17. The apparatus of claim 13, furthercomprising an adhesive disposed between the top and bottom portions ofthe carrier and configured to maintain the top and bottom portions at afixed distance apart from one another.
 18. The apparatus of claim 13,wherein the carrier is folded along a fold line to define a top portioncarrying the first conductive area and a bottom portion carrying thesecond conductive area.
 19. The apparatus of claim 18, wherein the firstand second conductive regions on the carrier are electrically isolatedfrom one another along the fold line.
 20. The apparatus of claim 18,wherein the opening is located along the fold line.
 21. The apparatus ofclaim 13, wherein the electrochemical module is located on a distal endof the carrier, and a proximal end of the carrier includes first andsecond contacts configured to establish a connection between the firstand second electrodes and an analyte measurement device.
 22. Theapparatus of claim 13, wherein the electrochemical module has opposedends mounted on the carrier, and a mid-portion located between theopposed ends and spaced a distance apart from the carrier.
 23. Theapparatus of claim 13, wherein the electrochemical module has a centralportion extending along a central axis and containing theelectrochemical cavity, and opposed end portions having central axesthat extend at an angle relative to the central axis of the centralportion.
 24. The apparatus of claim 13, wherein the carrier iselectrochemically non-functional.
 25. An electrochemical sensorapparatus, comprising: an electrochemical module having anelectrochemical cavity with first and second electrodes, and a samplereceiving chamber having a reagent layer configured to react with ananalyte of a fluid sample received in the electrochemical cavity; and acarrier having a top insulating substrate having a first conductiveregion, a bottom insulating substrate having a second conductive region,a distal cut-out extending through a distal end of the top and bottominsulating substrates, at least a portion of the electrochemical moduleextending across the distal cut-out such that the first electrode is inelectrical communication with the first conductive region and the secondelectrode is in electrical communication with the second conductiveregion, and a proximal cut-out extending through a proximal end of thebottom insulating substrate to expose a contact area on the firstconductive region of the top insulating substrate such that the firstcontact area and a second contact area on the bottom insulatingsubstrate are exposed to allow electrical connection with an analytemeasurement device to establish a connection between the first andsecond electrodes and the analyte measurement device.
 26. Anelectrochemical module, comprising: a first insulating substratecarrying a first electrode and a second insulating substrate carrying asecond electrode, the first and second insulating substrates each havingopposed sidewalls extending between first and second terminal ends, andan axis extending between the first and second terminal ends, and thefirst and second insulating substrates being offset from one anothersuch that a first terminal end of the first insulating substrate extendsa distance beyond a first terminal end of the second insulatingsubstrate to expose the first electrode, and a second terminal end ofthe second insulating substrate extends a distance beyond a secondterminal end of the first insulating substrate to expose the secondelectrode, and the first and second insulating substrates each having awidth extending between the first and second terminal ends that is atleast twice a length extending between the opposed sidewalls; at leastone spacer disposed between the first and second insulating substratesand maintaining the first and second electrodes in a spaced apartrelationship with one another; and an electrochemical cavity formedbetween the first and second electrodes and configured to receive afluid sample, the electrochemical cavity include a reagent configured toreact with an analyte of a fluid sample received in the electrochemicalcavity.
 27. The electrochemical module of claim 26, wherein the at leastone spacer comprises a first spacer positioned adjacent to the firstterminal end of the second insulating substrate, and a second spacerpositioned adjacent to the second terminal end of the first insulatingsubstrate.
 28. A carrier web, comprising: a carrier having first andsecond conductive areas electrically isolated from one another, and aplurality of openings spaced a distance apart from one another; and aplurality of electrochemical modules, each module being mounted acrossone of the plurality of openings, and each electrochemical module havinga first electrode in communication with the first conductive area, asecond electrode isolated from the first electrode and in communicationwith the second conductive area, and an electrochemical cavityaccessible through the opening in the carrier for receiving a fluidsample.
 29. The carrier web of claim 28, wherein the carrier includes alongitudinally extending fold line defining a top portion carrying thefirst conductive area and a bottom portion carrying the secondconductive area.
 30. A method for manufacturing an electrochemicalsensing apparatus, comprising: positioning opposed ends of anelectrochemical module on a carrier such that an electrochemical cavityformed in the electrochemical module is positioned across an openingformed in the carrier; and folding the carrier to engage the opposedends of the electrochemical module between top and bottom portions ofthe carrier.
 31. The method of claim 30, wherein the electrochemicalmodule includes a first insulating substrate carrying a first electrodethat is positioned in electrical contact with a first electricallyconductive region on the carrier, and a second insulating substratecarrying a second electrode that is positioned in electrical contactwith a second electrically conductive region on the carrier.
 32. Themethod of claim 30, further comprising, prior to positioning, formingfirst and second electrically conductive regions on the carrier suchthat the first and second electrically conductive regions areelectrically isolated from one another.
 33. The method of claim 32,wherein, when the carrier is folded, the first electrically conductiveregion is on the top portion of the carrier and the second electricallyconductive region is on the bottom portion of the carrier.
 34. Themethod of claim 30, further comprising, prior to folding, positioning aspacer on the carrier such that the spacer maintains the top and bottomportions at a distance apart from one another when the carrier isfolded.